Double-blind Trial Research Articles

Efficacy of Perineural Dexmedetomidine in Ultrasound-guided Interscalene Block on Rebound Pain after Shoulder Arthroscopy.

This prospective, randomized, double-blind trial was performed to investigate the effect on rebound pain incidence of mixing dexmedetomidine (DEX) with local anesthetics in a combined injection interscalene block (ISB) during shoulder arthroscopy. 47 patients were enrolled in this study. Patients were randomly assigned to 2 groups: Group DEX and Group Control received ultrasound-guided ISB using 12mL of 0.5% ropivacaine with 50ug of dexmedetomidine or without dexmedetomidine. Pain scores at 6, 12, 24, 48 h after surgery were assessed with Numeric Pain Rating Scale (NRS). Additional analgesic requirements and side effects in the first 48h postoperatively, as well as sleep disturbance on the night and other complications of surgery were examined. The incidence of rebound pain was lower in the group DEX than in the Control group. Perineural DEX decreased pain scores at 12 h and 24 h postoperatively. Group DEX had a prolonged time to first analgesic request, PCA sufentanil consumption in group DEX was less than group Control during the first 48 hours postoperatively. The number of patients with sleep disturbance and nausea and vomiting in the DEX group was lower on the first night postoperative. Perineural dexmedetomidine added to ISB exerts beneficial effect on the incidence of rebound pain after ISB in patients with pain catastrophizing undergoing shoulder arthroscopy. Perineural dexmedetomidine facilitated the implementation of multimodal analgesia in the early stage after operation.

Immediate effects of Kinesio taping on pain, proprioception, and posture in round shoulder individuals with subacromial impingement syndrome: A randomized, double-blinded controlled trial.

Round shoulder posture (RSP), characterized by forward shoulder positioning from weakened and tense muscles, disrupts normal biomechanics and can cause Subacromial impingement syndrome (SIS), resulting in pain during specific movements or positions. This study examines the immediate effects of Kinesio taping (KT) on pain, proprioception, and posture in individuals in round shoulder individuals with SIS. The study involved 114 patients diagnosed with RSP and SIS. Pain intensity was assessed using a Visual Analog Scale (VAS), proprioception was measured with an inclinometer, and posture was evaluated using The New York Posture Rating Chart (NYPRC). Participants were randomly assigned to experimental group (EG) (n = 57), which received KT application, or to sham group (SG) (n = 57), which underwent a sham procedure. KT was applied to the affected shoulder and scapular regions. Assessments were conducted both before and after the application of Kinesio tape. According to the study results, the differences in VAS scores (P = .002), proprioception abduction (P = .023) and NYPRC scores (P = .04), were statistically significant in the EG compared to the SG (P < .05). However, there was no significant difference in proprioception flexion between the groups (P > .05). KT demonstrates immediate benefits in reducing pain and improving scapular alignment in individuals with RSP and chronic shoulder pain. These findings underscore its potential effectiveness as a therapeutic intervention for managing symptoms associated with RSP and impingement syndrome, particularly in terms of pain relief and posture enhancement.

Evaluation of the safety, tolerability, pharmacokinetics and pharmacodynamics of SM17 in healthy volunteers: results from pre-clinical models and a first-in-human, randomized, double blinded clinical trial

BackgroundAlarmins mediate type 2 T helper cell (Th2) inflammation and serve as upstream signaling elements in allergic inflammation and autoimmune responses. The alarmin interleukin (IL)-25 binds to a multi-domain receptor consisting of IL-17RA and IL-17RB subunits, resulting in the release of Th2 cytokines IL-4, IL-5, IL-9 and IL-13 to drive an inflammatory response. Therefore, the blockage of IL-17RB via SM17, a novel humanized monoclonal antibody, offers an attractive therapeutic target for Th2-mediated diseases, such as asthma.MethodsWild-type mice were stimulated with house dust mite (HDM) extracts for evaluation of SM17’s pre-clinical efficacy in allergic asthma. The safety, pharmacokinectics (PK), pharmacodynamics (PD), and immunogenicity of intravenous (IV) doses of SM17 were assessed in a 2-part clinical study in healthy adult subjects. In Part A, 53 healthy participants were enrolled to receive a single IV dose of SM17 (2, 20, 70, 200, 400, 600, 1200 mg) or placebo. In Part B, 24 healthy subjects were enrolled to receive a single IV dose of SM17 every two weeks (Q2W; 200, 400, 600 mg) or placebo for a total of 3 doses.ResultsAnimal studies demonstrated that SM17 significantly suppressed Th2 inflammation in the bronchoalveolar lavage fluid and infiltration of immune cells into the lungs. In the Phase I clinical study, no drug-related serious adverse events were observed. Total SM17 exposure increased by approximately 60- to 188-fold with a 60-fold increase in dose from 20 to 1200 mg SM17. Upon administration of the third dose, mean accumulation ratios over 200-600 mg was 1.5 to 2.1, which confirms moderate accumulation of SM17. After Q2W dosing of SM17 over 4 weeks, total exposure increased in a dose-proportional manner from 200 mg to 600 mg SM17.ConclusionIn the pre-clinical studies, we demonstrated that SM17 is a potential therapeutic agent to treat allergic asthma. In the Phase 1 clinical trial, a single IV dose of SM17 up to 1200 mg and three Q2W doses up to 600 mg were well tolerated in healthy participants and demonstrated a favorable safety profile. The pre-clinical efficacy and clinical PK and immunogenicity results of SM17 support further clinical development.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT05332834.

Comparison of Hemodynamic Responses to Ketofol versus Etomidate During Anesthesia Induction in Elderly Patients

Background: Nausea While elderly patients are at an increased risk of perioperative morbidity and mortality; old age alone is not a contraindication for surgery. General factors that should be considered in preoperative risk assessments include age, functional status, cognition, nutritional status, and comorbidities, such as cardiac, pulmonary, renal, and endocrine disorders. Induction of anesthesia is a critical step in surgery, particularly for elderly patients and those with a high physical status. Commonly used drugs for this purpose include etomidate and propofol. Therefore, this study aimed to compare the impact of Ketofol versus etomidate alone on the hemodynamic status of patients who fall under the ASA class II or higher. Methods: The study was a prospective randomized double-blind clinical trial, with a study population of age of ≥65 years, ASA physical status class II or higher, that were randomized into two groups. Ketofol (n=45) and, Etomidate (n=45) groups. Patients followed for clinical outcomes including their hemodynamic status during the induction period. Results: The present study showed that, the examination of hemodynamic parameters up to 10 minute after laryngoscopy showed that none of these parameters were significantly different between the two groups, while immediately after anesthesia induction, heart rate and blood pressure were found to be significantly different. However, there was no significant difference in terms of SPO2 among the two groups in any given interval. Conclusion: The results of the present study revealed that Ketofol resulted in better regulation and stability of blood pressure and heart rate in patients undergoing endotracheal intubation, compared to etomidate alone.

Antifungal Efficacy of Ganoderma lucidum and Clotrimazole for Treatment of Denture Stomatitis: A Randomized Clinical Trial

Objectives: This study aimed to compare the antifungal efficacy of Ganoderma lucidum (G. lucidum) and clotrimazole for treatment of denture stomatitis (DS). Materials and Methods: This double-blind randomized clinical trial was conducted on 50 patients with DS types I and II assigned to two groups (N=25). In the first group, G. lucidum extract was administered in the form of 5% gel while 1% clotrimazole gel was prescribed for the second group. Pain intensity according to the visual analog scale (VAS), and the percentage of DS recovery based on the Budtz-Jorgenson index were evaluated and recorded after 7 and 14 days. Data were analyzed using the Chi-square test, independent samples t-test, repeated measures ANOVA, and logistic regression (alpha=0.05). Results: The percentage of complete recovery on day 7 in the G. lucidum group (28%) was higher than that in the clotrimazole group (16%) but not significantly (P=0.592). Not wearing dentures overnight significantly increased the odds of recovery by 6.56 times, while the odds of recovery decreased by 0.03 times in DS type II, as compared to DS type I (P= 0.009). Conclusion: No significant difference existed between the antifungal efficacy of G. lucidum and clotrimazole for clinical treatment of DS. Thus, Ganoderma may be regarded as an alternative treatment, especially in patients’ resistant to azoles. Nonetheless, further clinical studies are required to shed more light on this topic.

Trained dogs can detect canine urothelial carcinoma of the bladder

Dog have been trained to detect a variety of human cancers. However, studies examining their ability to find canine cancer are sparse and show variable results. Whilst dogs were shown to be successful at detecting malignant tumors from saliva samples, they were previously unsuccessful at finding canine urothelial carcinoma (UC) from urine. We used advanced training methods to explore if dogs can accurately detect urothelial carcinoma (UC) from canine urine.Urine samples from healthy dogs without urinary tract abnormalities (control), with non-malignant urinary tract disease (control), and with UC (positive) were collected prospectively. Urothelial carcinoma was diagnosed using cytology and/or histopathology. All dogs were naïve of chemotherapy, underwent bladder ultrasound and urinalysis. Residual urine remaining after conventional diagnostic procedures was frozen in glass jars until analysis and used for dog training and testing.Three dogs previously trained to detect human cancer underwent up to 29 days of additional training. They were each presented with 20 control samples (from either 13 or 14 unique individuals), 10 UC positive samples (from between 5 and 7 individuals), in a double-blind trial and their behavioral responses recorded.When considering only unique donor dogs, a mean of 66.7% (range 40–85.7%) of UC were correctly indicated and a mean of 87.5% (range 78.6–92.3%) were correctly ignored. The overall sensitivity (considering all samples) was 80% (range 70–90%), and specificity was 91.7% (range 85–95%). This study suggests that, when using appropriate methods, dogs can be trained to detect canine UC from urine and could serve as an additional non-invasive diagnostic test for the disease.

The additional effect of 5% atorvastatin shampoo in the treatment of adult patients with mild to moderate seborrheic dermatitis of the scalp: A prospective, randomised, double-blind trial

Background Seborrheic dermatitis (SD) is a long-lasting inflammatory skin condition that predominantly impacts regions abundant in sebaceous glands, including the scalp. Objectives To assess the efficacy and anti-inflammatory effect of atorvastatin as an additive treatment among SD patients. Materials and Methods In a prospective, randomised, double-blind trial, 46 patients over 18 years old with mild to moderate scalp SD were randomly assigned to receive either 2% ketoconazole shampoo or 2% ketoconazole shampoo plus 5% atorvastatin. The severity of dermatitis was assessed based on the symptom scale of seborrheic dermatitis (SSSD), and the variables of erythema, scaling, and itching, at baseline and 4 weeks after the intervention. Results Based on our analyses, both treatment methods significantly reduced the SSSD scores. However, the average SSSD score in patients using ketoconazole shampoo plus atorvastatin decreased by an average of five points after 1 month. This reduction was comparable to the average decline of 3.5 points observed in the group using ketoconazole shampoo alone. Specifically, the severity of dermatitis, as assessed by the SSSD score, significantly decreased by 1.92 points more, in individuals using the atorvastatin-containing shampoo compared to the comparison group (P = 0.02). Limitation This research was conducted at a single centre which limits the validity of the findings. Conclusion The results of this study suggest that shampoo containing atorvastatin provides a statistically significant effect compared to ketoconazole shampoo alone, indicating its potential as an alternative treatment for SD. The treatment notably alleviates symptoms associated with scaling and itching which are the common manifestations of the condition.

A randomized double-blind noninferiority clinical multicenter trial on oral moxifloxacin versus placebo in the outpatient treatment of uncomplicated acute appendicitis: APPAC IV study protocol.

Antibiotic therapy is currently considered a safe and effective treatment alternative for computed tomography (CT)-confirmed uncomplicated acute appendicitis with recent studies reporting good results on both oral antibiotics only and outpatient management. Furthermore, there are promising pilot results on uncomplicated acute appendicitis management with symptomatic treatment (placebo). This trial aims to assess whether both antibiotics and hospitalization can be safely omitted from the treatment of uncomplicated acute appendicitis. The APPAC IV (APPendicitis Acuta IV) trial is a randomized, double-blind, multicenter noninferiority clinical trial comparing oral moxifloxacin with oral placebo in an outpatient setting with a discharge directly from the emergency room (ER). Adult patients (18-60 years) with CT-confirmed uncomplicated acute appendicitis (absence of appendicolith, abscess, perforation, tumor, appendiceal diameter ⩾15 mm on CT, or body temperature >38 °C) will be enrolled in nine Finnish hospitals. Primary outcome is treatment success at 30 days, that is, the resolution of acute appendicitis resulting in discharge from the hospital without appendectomy during the 30-day follow-up evaluated using a noninferiority design with a noninferiority margin of 6 percentage points. Noninferiority will be evaluated using one-sided 95% confidence interval of proportion difference between groups. Secondary endpoints include postintervention complications, recurrent appendicitis after the 30-day follow-up, duration of hospital stay, admission to hospital and reason for admission, readmissions to emergency department or hospitalization, VAS pain scores, quality of life, sick leave, and treatment costs. The follow-up after discharge from the ER includes a phone call at day 1, and at 3-4 days, 30 days, and 1, 3, 5, 10, and 20 years. Those eligible patients, who decline to undergo randomization, will be invited to participate in a concurrent observational cohort study with follow-up at 30 days, and 1 and 5 years. To our knowledge, APPAC IV trial is the first large randomized, double-blind, noninferiority multicenter clinical trial aiming to compare oral antibiotics and placebo for CT-diagnosed uncomplicated acute appendicitis in an outpatient setting. The study aims to bridge the major knowledge gap on whether antibiotics and hospitalization or both can be omitted in the treatment of uncomplicated acute appendicitis. The study protocol has been approved by the Clinical Trials Information System (CTIS) of the European Medicines Agency (EMA), study number: 2023-506213-21-00 and the trial has been registered in ClinicalTrials.gov, NCT06210269.

Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic

The psychological morbidity experienced by physicians, advanced practice practitioners (APPs), and nurses from working during the COVID-19 pandemic includes burnout, depression, and posttraumatic stress disorder (PTSD). To investigate whether psilocybin therapy could improve symptoms of depression, burnout, and PTSD in US clinicians who developed these symptoms from frontline clinical work during the pandemic. This double-blind randomized clinical trial enrolled participants from February to December 2022. Participants included physicians, APPs, and nurses who provided frontline care for more than 1 month during the pandemic and had no prepandemic mental health diagnoses but had moderate or severe symptoms of depression at enrollment. Participants were randomly assigned to either the psilocybin or niacin arm. Data analysis was conducted between December 2023 and May 2024 and was based on the intention-to-treat principle. One intervention episode consisted of 2 preparation visits, 1 medication session, and 3 integration visits. At the medication session, participants received psilocybin, 25 mg, or niacin, 100 mg, orally. The primary outcome was a change from baseline (preparation 1 session) to day 28 (after medication administration) in symptoms of depression as measured by the clinician-administered Montgomery-Asberg Depression Rating Scale (MADRS) used by blinded raters. The secondary outcomes were a change in symptoms of burnout (measured with the Stanford Professional Fulfillment Index [SPFI]) and symptoms of PTSD (measured with the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]). A total of 30 clinicians (15 females [50%]; mean [range] age, 38 [29-60] years) participated, of whom 15 were randomly assigned to receive psilocybin and 15 to receive niacin. The mean change in symptoms of depression (MADRS scores) from preparation 1 session to day 28 was -21.33 (7.84) in the psilocybin arm compared with -9.33 (7.32) in the niacin arm, with a mean difference between arms of -12.00 (95% CI, -17.67 to -6.33; P < .001), a decrease in MADRS scores indicating improvement. The mean change in SPFI scores from preparation 1 session to day 28 showed a numerically larger improvement in symptoms of burnout in the psilocybin compared with the niacin arm (-6.40 [5.00] vs -2.33 [5.97]; P = .05) but was not statistically significant. Since the SPFI score change did not reach statistical significance, the PCL-5 score change was evaluated descriptively. The mean change in PCL-5 scores showed a numerically larger decrease in symptoms of PTSD from preparation 1 session to day 28 in the psilocybin vs the niacin arm (-16.67 [15.04] vs -6.73 [10.69]), but this difference was not statistically tested. This randomized clinical trial found that psilocybin therapy resulted in a significant, sustained reduction in symptoms of depression experienced by clinicians after frontline work during the COVID-19 pandemic. The findings establish psilocybin therapy as a new paradigm of treatment for this postpandemic condition. ClinicalTrials.gov Identifier: NCT05163496.

Clinical evaluation of AYUSH-SL in patients receiving mass drug administration for the treatment of chronic inflammatory lymphedema, a double blind, placebo controlled, multicentric study.

A 2.5-year placebo controlled double blind trial was conducted to investigate the safety and efficacy of AYUSH- SL, a poly- herbal Ayurvedic formulation on filarial lymphedema in different endemic areas of India. Lymphatic filariasis (LF) is caused by parasitic nematodes from Wuchereria bancrofti, Brugia malayi, or B. timori that are transmitted through mosquitoes. In Ayurveda, LF has been elaborately narrated under the heading Shlipada, and the literature also includes detailed therapeutic measures. The multicenter, prospective, parallel group interventional study of a total of 180 participants were recruited within the duration through competitive enrollment. Diagnosed cases of grade I and grade II filarial lymphedema of Grade I and Grade II (lower extremities) were included in the trial. The study group was treated with MDA and AYUSH-SL or its placebo tablet. The control group had received MDA and a matching placebo. The primary outcome measure was the reduction in edema calculated for analysis by percentage reduction from baseline at the 4th, 12th and 24th week. Secondary outcome measures included improved quality of life (QoL), which was assessed using the Lymphatic Filariasis Specific QoL Questionnaire, and prevention of recurrence of acute episodes, which was evaluated by investigating the presence and severity of episodes in the past 4 weeks. The water displacement method for the evaluation of the efficacy of the intervention was shown to be highly significant compared to the baseline value (right leg; 3071.60 ± 970.482, 2828.40±829.339, p<0.001and Left leg; 3158.69 ± 1136.391, 2890.73 ±1077.475, p<0.001). There was significant improvement of Quality of Life in the LF QoL Questionnaire (p <0.001) at each follow-up visit in both groups. Safety estimations on hematologic and biochemical parameters were within limits and or changes were not significant. The results revealed that AYUSH- SL is safe and effective for FL due to its comprehensive anti-inflammatory, antimicrobial, and anti-allergic activities.

Color evaluation of a one-shade used for restoration of non-carious cervical lesions: an equivalence randomized clinical trial

BackgroundObtaining a perfect color match with resin composite presents a significant challenge. The chameleon effect has enabled resin composite to mimic the color of the adjacent tooth structure in vitro. This double-blind, split-mouth and equivalent randomized clinical trial evaluated the color matching of one-shade resin composite with chameleon effect versus multi-shade resin composite in non-carious cervical lesion restorations (NCCLs).MethodsOne hundred twenty restorations were performed on NCCLs with two restorative materials (n = 60). After prophylaxis, the teeth were isolated with rubber dam and one universal adhesive was applied in the selective enamel etching strategy. For both groups, the restorations were inserted incrementally. The values of ΔEab and ΔE00 in the cervical and middle third were evaluated using a digital spectrophotometer before vs. after the restorations. The restorations were evaluated at baseline and after 7 days, 6-, 12- and 18-month of clinical performance according to the FDI criteria (Word Federation Criteria). Statistical analysis was performed using Chi-square test for all parameters. Color change was analyzed by two one-sided t-tests for paired samples (α = 0.05).ResultsRegarding the color measurement no significant difference was observed when Vittra APS (FGM Dental Products, Joinville, SC, Brazil) was compared to Vittra Unique (FGM Dental Products, Joinville, SC, Brazil) for any of the comparisons performed (p > 0.05). However, the ΔEab and ΔE00 values for the cervical third, both before and after the restorations, were higher compared to the ΔEab and ΔE00 values observed when comparing the cervical and middle thirds after the restorations. After 18 months, five restorations exhibited minimal discrepancies in terms of marginal adaptation or marginal discoloration (p > 0.05). In all other criteria, including retention rate, no changes were detected at the 18-month recall.ConclusionsThe one-shade resin composite used achieve the same color match when compared to a multi-shade resin composite after a period of 7 days in NCCLs. Overall, the restorations scored clinically very good (FDI) at baseline and after 18 months for all outcomes.Clinical SignificanceThe use of a one-shade resin composite in NCCLs can be recommended because it has the ability to simplify the restoration procedure and maintaining an excellent clinical performance.Registration of clinical trialsRBR-8txr4fw: 26/05/2022.

Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia: A Randomized Clinical Trial.

Fostamatinib, a spleen tyrosine kinase inhibitor, has been reported to improve outcomes of COVID-19. To evaluate the efficacy and safety of fostamatinib in adults hospitalized with COVID-19 and hypoxemia. This multicenter, phase 3, placebo-controlled, double-blinded randomized clinical trial was conducted at 41 US sites and 21 international sites between November 17, 2021, and September 27, 2023; the last follow-up visit was December 31, 2023. Participants were adults aged 18 years or older hospitalized with acute SARS-CoV-2 infection and hypoxemia. Data were analyzed between January 10 and March 8, 2024. Fostamatinib, 150 mg orally twice daily for 14 days, or placebo. The primary outcome was oxygen-free days, an ordinal outcome classifying a participant's status at day 28 based on mortality and duration of supplemental oxygen use. An adjusted odds ratio (AOR) greater than 1.0 was considered to indicate superiority of fostamatinib over placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included elevated transaminase values, neutropenia, and hypertension. Of the 400 participants randomized (median age, 67 years [IQR, 58-76 years]; 210 [52.5%] men), 199 received fostamatinib and 201 received placebo. The mean (SD) number of oxygen-free days was 13.4 (12.4) in the fostamatinib group and 14.2 (12.1) in the placebo group (unadjusted mean difference, -1.26 days [95% CI, -3.52 to 1.00 days]; AOR, 0.82 [95% credible interval (CrI), 0.58-1.17]). Mortality at 28 days occurred in 22 of 195 patients (11.3%) in the fostamatinib group and 16 of 197 (8.1%) in the placebo group (AOR, 1.44; 95% CrI, 0.72-2.90). Aspartate aminotransferase elevation occurred more commonly in the fostamatinib group (23 [11.6%]) than in the placebo group (11 [5.5%]; AOR, 2.28; 95% CrI, 1.07-4.84). Other safety outcomes were similar between groups. In this randomized clinical trial of adults hospitalized with COVID-19 and hypoxemia, fostamatinib did not increase the number of oxygen-free days compared with placebo. These results do not support the hypothesis that fostamatinib improves outcomes among adults hospitalized with hypoxemia during the Omicron era. ClinicalTrials.gov Identifier: NCT04924660.

Comparison of Ultrasound-Guided Hydrodissection with Various Volumes of 5% Dextrose for Carpal Tunnel Syndrome: A Prospective Randomized Controlled Double-Blind Trial.

Ideal volume of 5% dextrose (D5W) for median nerve hydrodissection (HD) for treating carpal tunnel syndrome (CTS) is still unknown. This study assessed the efficacy of nerve hydrodissection using varying volumes of D5W for treating mild to moderate CTS. Eighty participants with unilateral mild to moderate CTS were randomized into groups to receive either 5 ml of normal saline (NS), 5 ml of D5W, 10 ml of NS, and 10 ml of D5W, with each group undergoing one session of ultrasound-guided HD. Visual Analogue Scale (VAS), Boston Carpal Tunnel Syndrome Questionnaire (BCTQ), grip and pinch strength, cross-sectional area (CSA) of median nerve, and electrophysiological assessment were performed at baseline and weeks 4 and 12. In the 10 ml D5W group, VAS scores considerably improved compared with those in the NS groups. Although nerve CSA values decreased in all groups during follow-ups, the 10 mL D5W group showed a statistically significant improvement compared to the NS groups by the 12th week (p ≤ 0.01). Ultrasound-guided median nerve HD with 10 ml D5W was more effective in reducing pain and nerve size than the NS groups at the 12th week.

Efficacy and Safety of Dose Increase From 40 mg/d to 80 mg/d of Lurasidone in Patients With Schizophrenia: A Post Hoc Analysis of Extension Trial.

The primary objective of this study was to evaluate the efficacy and safety of increasing the dose of lurasidone from 40 mg/d to 80 mg/d in patients with schizophrenia. This post hoc analysis focused on patients who completed a 6-week double-blind, placebo-controlled trial of lurasidone and transitioned to a subsequent 12-week open-label extension trial. Patients initially assigned to lurasidone (40 mg/d) or placebo during the double-blind trial (DBT-LUR group or DBT-PLA group, respectively) received lurasidone (40 mg/d) during the extension. Clinicians could increase the dose to 80 mg/d based on clinical judgment. The efficacy outcomes included the change in the Positive and Negative Syndrome Scale (PANSS) total score from the start to the end of the lurasidone (80 mg/d) treatment period. Safety outcome was the rate of newly emergent adverse events. Of 287 patients in the intention-to-treat population, 153 received an increased dose of lurasidone from 40 mg/d to 80 mg/d. Significant reductions in the PANSS total scores were observed in both groups (all P values, ≤0.001). Additionally, 35.9% of the DBT-LUR group and 40.0% of the DBT-PLA group achieved a ≥20% reduction in the PANSS total score. New adverse events emerged in 47.4% of the DBT-LUR group and 48.0% of the DBT-PLA group during the lurasidone (80 mg/d) treatment period. Increasing the dose of lurasidone from 40 mg/d to 80 mg/d may be effective and well tolerated in patients with schizophrenia. Because of the lack of a control group and blinding, the results should be interpreted with caution.

Ginkgo biloba for Tardive Dyskinesia and Plasma MnSOD Activity: Association with MnSOD Ala-9Val Variant: A Randomized, Double-blind Trial.

Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia (TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing antioxidant enzymes such as mitochondrial manganese superoxide dismutase (MnSOD). This study examined whether EGb761 treatment would improve TD symptoms and increase MnSOD activity, particularly in TD patients with specific MnSOD Val-9Ala genotype. An EGb761 (240 mg/day) 12-week double-blind clinical trial with 157 TD patients was randomized. The severity of TD was measured by the Abnormal Involuntary Movement Scale (AIMS) and plasma MnSOD activity was assayed before and after 12 weeks of treatment. Further, in an expanded sample, we compared MnSOD activity in 159 TD, 227 non-TD and 280 healthy controls, as well as the allele frequencies and genotypes for the MnSOD Ala-9Val polymorphism in 352 TD, 486 non-TD and 1150 healthy controls. EGb761 significantly reduced TD symptoms and increased MnSOD activity in TD patients compared to placebo (both p < 0.01). Moreover, we found an interaction between genotype and treatment response (p < 0.001). Furthermore, in the EGb761 group, patients carrying the Ala allele displayed a significantly lower AIMS total score than patients with the Val/Val genotype. In addition, MnSOD activity was significantly lower at baseline in TD patients compared with healthy controls or non-TD patients. EGb761 treatment enhanced low MnSOD activity in TD patients and produced greater improvement in TD symptoms in patients with the Ala allele of the MnSOD Ala-9Val polymorphism.

Vascular Endothelial Effects of Sacubitril/Valsartan in Heart Failure With Reduced Ejection Fraction: Randomized Controlled Trial

BackgroundThe mechanism of how sacubitril/valsartan improves outcomes in heart failure with reduced ejection fraction (HFrEF) is still incompletely understood. ObjectivesThe aim of this trial was to delineate the effects of sacubitril/valsartan on endothelial function, retinal microvascular function, and arterial stiffness in HFrEF. MethodsThis double-blind controlled trial randomized 79 stable HFrEF patients with NYHA class II-IV on guideline-recommended therapy (mean age: 59.4 ± 12 years, left ventricular ejection fraction: 30% ± 7%) to sacubitril/valsartan or valsartan alone for 3 months. The primary endpoint was flow-mediated vasodilation (FMD). Secondary outcomes included flicker-induced dilatation of retinal arterioles and venules (FIDv), retinal arteriovenous ratio, and surrogate markers of arterial stiffness (pulse wave velocity and augmentation index). ResultsThe primary outcome FMD did not significantly differ between sacubitril/valsartan and valsartan alone (FMD 6.6% ± 3.9% vs 6.7% ± 2.8%; ANCOVA coefficient adjusted for baseline values 0.36, 95% CI: −0.78 to 1.51, P = 0.53). The secondary outcomes flicker-induced dilatation of retinal arterioles, arteriovenous ratio, pulse wave velocity, and augmentation index showed no significant differences. FIDv was lower after sacubitril/valsartan versus valsartan alone (FIDv 2.4% ± 1.3% vs 3.1% ± 2.1%; ANCOVA coefficient −0.7, 95% CI: −1.4 to −0.02, P = 0.04). Systolic blood pressure was lower after sacubitril/valsartan versus valsartan alone (ANCOVA coefficient −6.5 mm Hg, 95% CI: −12.7 to −0.3 mm Hg, P = 0.04). There were numerically fewer serious adverse events with sacubitril/valsartan versus valsartan alone. ConclusionsIn this randomized double-blind clinical trial addressing mechanisms, sacubitril/valsartan lowered blood pressure and flicker-induced dilatation of retinal venules in patients with symptomatic HFrEF but did not improve endothelial function, retinal microvascular function, or arterial stiffness compared to valsartan monotherapy. (Differential Vascular and Endocrine Effects of Valsartan/​Sacubitril in Heart Failure With Reduced Ejection Fraction [VASCEND]; NCT03168568)

Do ankle braces affect functional performance? A randomised double-blinded cross-over trial

ObjectivesTo compare the effects of the KISS ankle brace, Aircast ankle brace, and no brace condition, on functional performance measures and perceptions of stability, confidence and reassurance in people with and without chronic ankle instability. DesignRandomised double-blinded cross-over trial. MethodA total of 42 participants (21 uninjured and 21 with chronic ankle instability) were recruited from the general population and completed a series of functional performance tests, including side hop (seconds), Star excursion balance test reach distance, triple hop for distance (centimetres), modified T-agility test (seconds), standing and maximum vertical jump reach (centimetres), while wearing two ankle brace conditions and no brace (control). Results were recorded and analysed by a blinded investigator. ResultsThere was no significant difference between conditions for average time on the side hop test (F(2,122) ​= ​0.04, P ​= ​0.96); best reach distance on SEBT in anterior (F (2,122) ​= ​0.04, P ​= ​0.96), postero-medial (F(2,122) ​= ​0.08, P ​= ​0.93) and postero-lateral (F(2,122) ​= ​0.08, P ​= ​0.92) directions; best distance performed on the triple hop (F(2,122) ​= ​0.03, P ​= ​0.97); best standing vertical jump performance (F(2,110) ​= ​0.04, P ​= ​0.97); best maximum vertical jump performance (F(2,110) ​= ​0.01, P ​= ​0.99); or best time for the modified T-agility run (F(2,122) ​= ​1.61, P ​= ​0.21). ConclusionsPractitioners can be assured that functional and balance performances will not be impacted by wearing an ankle brace.

Efficacy and safety of crocin supplementation in patients with central serous chorioretinopathy, a pilot randomized double blinded clinical trial

Efficacy and safety of crocin supplementation in patients with central serous chorioretinopathy, a pilot randomized double blinded clinical trial

Lactoferrin in the treatment of interstitial cystitis: a retrospective pilot study.

Interstitial cystitis (IC), defined as a painful bladder syndrome (PBS), is a chronic condition that manifests itself as a suprapubic pain associated with an enhancing of frequency/urgency of urination, and for which there is no cure. Here, we present a retrospective pilot study on women affected from IC/PBS and treated with bovine lactoferrin (bLf). A total of 31 women, affected (20) or unaffected (11) from hereditary thrombophilia (HT), presented the median of 6 episodes of IC/PBS during the 6 months before the study. Treatment consisted of 17 weeks of orally administered Valpalf® capsules, containing bLf plus sodium bicarbonate and citrate. Out of 31 patients, only 3 women had one episode of IC/PBS during the follow-up period, while no episode was observed in 28 women. In the HT group, a significant decrease in both serum IL-6 and D-dimers was found after Valpalf® treatment. Moreover, in Valpalf®-treated women, cystoscopy revealed a global improvement in the appearance of the bladder, especially in term of inflammation/irritation and presence of Hunner ulcers. Even if our results must be corroborated by randomized double-blinded controlled trials on a larger number of patients, our observations indicate that bLf treatment is efficient in relieving IC/PBS symptoms, without side effects.

The Effectiveness of a Poly-herbal Formulation from Traditional Persian Medicine (TPM) in Gastroesophageal Reflux Disease (GERD), a Double-Blinded Randomized Clinical Trial

Introduction:: Gastroesophageal reflux disease (GERD) leads to increased contact of the acidic refluxate with the esophageal mucosa. Nearly 10- 20 % of the world's population is affected by GERD. Due to the complications associated with GERD, as well as complications of long-term treatment with current medications, and global demand toward Complementary and Alternative Medicine (CAM), this study evaluated the efficacy of a poly-herbal formulation known as Mastic pill (Habb-e-Mastaki) from traditional Persian medicine (TPM), previously reformulated and standardized, in a double-blinded randomized clinical trial. Method:: 34 patients in the drug group received 4 capsules of Mastic pill plus Omeprazole capsule 20 mg daily. 34 patients in the placebo group received the same dosing of Omeprazole and placebo. The medication was given to patients for a total duration of 4 weeks. All patients were requested to fill out the modified GERD-HRQL questionnaire at the beginning and every two weeks for a total duration of six weeks. Result:: Reflux, and heartburn severity score as well as disruption of personal life score significantly reduced in both groups, but it was more remarkable in the drug group (P-value = 0.0001). Dysphagia, early satiation, and nausea significantly reduced in the drug group while the placebo group showed no improvement. Our results suggest that constipation, bloating, belching, and odynophagia did not significantly improve in none of the groups. Conclusion:: This study showed that Habb-e-Mastaki is effective against GERD. Further detailed in vitro and in vivo studies aimed at discovering the mechanism of action of this formulation and clinical studies involving a larger population will be necessary to explain and confirm the results obtained in the present study.